KEY TAKEAWAYS
- The BRCA1/2 trial aimed to evaluate the newly diagnosed PDAC patients other for HPC-associated mutations.
- Researchers used the 84-gene Invitae Multi-Cancer Panel to test for germline mutations.
- The study found BRCA1/2 mutations were rare in Mexican patients with PDAC. Universal germline testing was recommended.
The prevalence of pathogenic germline variants (PGVs) in Mexican patients with pancreatic ductal adenocarcinoma (PDAC) is not well-known. Researchers aimed to test a cohort of newly diagnosed PDAC patients for BRCA1/2 and other hereditary pancreatic cancer (HPC)-associated mutations.
The ethics committees at each institution (INCMNSZ, INCAN, and CM ABC Observatorio) approved the protocol. The study included individuals aged > 18 years diagnosed with PDAC within 6 months. Participants were enrolled continuously, irrespective of age, personal/family cancer history, hereditary cancer syndrome knowledge, or disease stage. The 84-gene Invitae Multi-Cancer Panel was used for genetic analysis. Patient attributes and family history were summarized via descriptive statistics (IBM SPSS Statistics Version 25).
Between August 2020 and June 2022, 119 newly diagnosed PDAC patients were identified. Among them, 107 were included, with 58% being women and a median age of 63. Clinical stages at diagnosis were Stage I (24%), Stage II (22%), Stage III (6%), and Stage IV (48%). All patients except one (Ashkenazi Jewish) had Hispanic ancestry. Only 7.5% (n = 8) had a prior history of different cancers, mainly breast cancer (N = 3). Around 62% had a family history of any cancer, 47.6% had a first-degree relative (FDR) with any cancer, 11% (n = 12) had a family history of pancreatic cancer (PC), while 9% (n = 10) had an FDR with PC. Clinically, 5 patients met hereditary cancer syndrome criteria familial pancreatic cancer (4) and Lynch syndrome (1). Pathogenic gene variants (PGVs) were found in 17.8% (n = 19) of patients. The prevalence of PGVs related to autosomal dominant PC risk was 11.2%: CDKN2A (5.6%), ATM (3.7%), BRCA2 (0.93%), and MSH6 (0.93%). Two patients had PGVs linked to autosomal dominant predisposition to other cancers (CHECK2 and NF1). Around 5.6% (n = 6) had PGVs associated with autosomal recessive syndromes elevating rare cancer risks other than PDAC (MUTYH, RECQL4, FH, and WRN). Researchers also detected variants of uncertain significance in 42% of patients.
The study concluded that BRCA1/2 mutations were not a significant risk factor for pancreatic cancer in Mexican patients. Universal germline testing using a comprehensive gene panel was recommended, and selective testing for BRCA1/2 was discouraged.
Source: https://meetings.asco.org/abstracts-presentations/219322
Clinical Trial: https://clinicaltrials.gov/study/NCT05305001
Vanessa Rosas Camargo, Jazmin Arteaga, Javier Melchor Ruan, Salvador Escorza, Alberto Cedro-Tanda, Silvia Vidal, Lucero Itzel Torres Valdiviezo, Miriam Heidi Cisneros Cordero, Cesar Arce Sandoval, Mónica Isabel Meneses Medina, Marytere Herrera, and Fidel David David Huitzil Melendez. Journal of Clinical Oncology 2023 41:16_suppl, 10609-10609.
